CP-KETOLAC 30

Indications

• Management of moderate to severe pain
• Post-operative pain relief
• Short-term treatment of pain when oral therapy is not possible

Dosage

Adults: For adults, the initial dose is typically 10 mg

Mechanism of action

Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to its mechanism of action. It is a non-selective inhibitor of both COX-1 and COX-2 enzymes, with clinical efficacy primarily derived from its inhibition of COX-2. This enzyme converts arachidonic acid to prostaglandins, mediators of inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation.

Pharmacodynamics

As a non-selective NSAID, ketorolac acts by inhibiting COX-1 and COX-2 enzymes. COX-1 is constitutively active and present in various tissues, while COX-2 is inducible and primarily involved in inflammatory responses. While inhibition of COX-2 leads to the desired anti-inflammatory and analgesic effects, inhibition of COX-1 is associated with increased risks of gastrointestinal bleeding, ulceration, and other serious side effects. Therefore, ketorolac is recommended for short-term use only.

Pharmacokinetics

Ketorolac is well-absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a volume of distribution of approximately 0.15 L/kg and is metabolized primarily in the liver via glucuronidation and hydroxylation. The elimination half-life is about 5 to 6 hours in healthy adults, and the drug is excreted mainly in urine, with about 90% of the dose recovered as metabolites.

Contra-indications

• Active or history of peptic ulcer disease
• History of gastrointestinal bleeding or perforation
• Severe renal impairment
• Hypersensitivity to ketorolac or other NSAIDs
• Concurrent use with other NSAIDs
• Labor and delivery
• Active bleeding conditions

Adverse effects

• Gastrointestinal bleeding
• Peptic ulcers
• Perforation of the gastrointestinal tract
• Renal impairment
• Cardiovascular events
• Headache
• Dizziness
• Nausea
• Abdominal pain

Interactions

• Anticoagulants (increased risk of bleeding)
• Other NSAIDs (increased risk of adverse effects)
• Lithium (reduced renal clearance)
• Methotrexate (increased toxicity)
• Diuretics (reduced effectiveness)

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor renal function in long-term use
• Caution in the elderly due to increased risk of adverse effects
• Avoid in patients with a history of asthma or allergic reactions to NSAIDs

Pregnancy

Use is contraindicated during pregnancy, especially in the third trimester due to the risk of fetal harm and complications during delivery.

Breast-feeding

Caution is advised; ketorolac is excreted in breast milk and may affect the nursing infant.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Tablets
• Injection solution

Indications

• Metabolic acidosis
• Severe hyperkalaemia
• Renal artery stenosis
• Nephrotic syndrome
• Severe heart failure
• Potassium depletion due to diuretics

Dosage

Children: Dosing in children should be appropriate to the body weight and clinical

Adults: Dosage must be tailored to the individual patient's acid-base status and clinical condition. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Trometamol is a weak base that functions as a proton acceptor. Upon intravenous administration, it binds to hydrogen ions and associated acid anions, leading to their excretion in urine. It is capable of combining with lactic, pyruvic, and other metabolic acids, thereby reducing hydrogen ion concentration in the body. The drug's ionized form predominates at physiological pH, allowing it to penetrate cell membranes and interact with intracellular acids. This action increases bicarbonate concentration and decreases carbon dioxide tension, potentially leading to hypoventilation.

Pharmacodynamics

Trometamol reduces acidity in the body by acting on acid-base buffers, thus shifting the balance towards alkalinity. It increases the flow of alkaline urine, enhancing diuresis and electrolyte excretion. The correction of metabolic acidosis can improve various physiological functions, but caution is required due to the potential for respiratory depression caused by decreased carbon dioxide tension.

Pharmacokinetics

Trometamol is administered intravenously and rapidly distributes into extracellular fluids. It is metabolized primarily in the liver, with renal excretion of the resultant salts. The onset of action is typically quick, and the duration of effect depends on the severity of acidosis and the therapeutic context. Monitoring of plasma potassium levels is essential, particularly in patients with renal impairment.

Contra-indications

• Anuria
• Chronic respiratory acidosis

Adverse effects

• Hepatic necrosis in neonates
• Hypoglycaemia
• Respiratory depression

Interactions

• Potassium salts may cause nausea and vomiting
• Drugs exacerbating hyperkalaemia should be reviewed and stopped as appropriate

Precautions

• Extravasation can cause severe tissue damage
• Use with caution in renal impairment due to risk of hyperkalaemia

Pregnancy

Limited information available, management of hyperkalaemia may harm fetus.

Breast-feeding

No information available.

Storage

Store in a cool, dry place. Protect from light.

Formulations

• Solution for infusion (Trometamol 363.4 mg per 1 ml, Tris 36.34% solution for infusion)

Mechanism of action

Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action. Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the "S" enantiomer is largely responsible for it's pharmacological activity.

Pharmacodynamics

Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations.

Mechanism of action

Tromethamine is an alkalinizing agent which acts as a proton (hydrogen ion) acceptor. Tromethamine is a weak base; following IV injection, it attracts and combines with hydrogen ions and their associated acid anions and the resulting salts are excreted in urine. Tromethamine can combine with lactic, pyruvic, and other metabolic acids and with carbonic acid. ... At pH 7.4, approximately 70% of the tromethamine present in plasma is in the ionized (protonated) form; if pH is decreased from pH 7.4, the ionized fraction of the drug is increased. In contrast to the ionized fraction of tromethamine, which upon administration reacts only with acid in the extracellular fluids, the fraction of the dose which remains un-ionized at physiologic pH is thought to be capable of penetrating the cell membrane to combine with intracellular acid. Since administration of tromethamine reduces hydrogen ion concentration, there is a decrease in proton donor and an increase in proton acceptor concentrations in body buffers. In the bicarbonate:carbonic acid buffer, the concentration of dissolved carbon dioxide is decreased (at least until regulatory mechanisms compensate) and the concentration of bicarbonate is increased. The reduction of carbon dioxide tension removes a potent stimulus to breathing and may result in hypoventilation and hypoxia. Tromethamine ... acts as a weak, osmotic diuretic, increasing the flow of alkaline urine containing increased amounts of electrolytes. By removing protons from hydronium ions, ionization of carbonic acid is shifted so as to decrease pCO2 and to increase bicarbonate. Excess bicarbonate is then gradually excreted in kidney. /Tromethamine is an/ especially useful way to manage excessively high pCO2 in respiratory acidosis...